Abstract 73: Preclinical evaluation of chemoradiation with cetuximab HPV-positive head and neck cancer suggests significant radiosensitization

PURPOSE: Whether cetuximab, a monoclonal antibody to the epidermal growth factor receptor, should be combined with radiation in patients with human papillomavirus (HPV) positive locally advanced head and neck cancer (HNC) is not known. Currently available data are inadequate to address this important therapeutic question. We sought to examine the ability of cetuximab to act as a radiosensitizer and to examine the mechanism of action of this combination in a model system of HPV+ HNC. METHODS: Four cell lines (UD-SCC2, UM-SCC47, UPCI-SCC90, 93-VU-147T) validated for HPV expression were used for all assays. Subcutaneous flank xenografts were performed in Hsd:athymic Nude-Foxn1nu female mice treated with intraperitoneal cetuximab (0.2mg/mouse) or flank radiation (2 Gy/fraction) delivered twice weekly for 2 weeks. Time to tumor quadrupling from baseline was assessed by Kaplan-Meier method. Flow cytometry was used to assess apoptosis by Annexin V staining and cell cycle distribution by propidium iodide staining. RESULTS: While there was minimal in vitro radiosensitization after treatment with cetuximab (similar to that seen in HPV-negative HNC), cetuximab + radiation resulted in a significant increase in time to tumor quadrupling compared to cetuximab alone (p=0.001) or radiation alone (p